The transferrin receptor is a cell surface protein associated with cell proliferation and identified in neoplastic breast tissue at elevated levels compared to the normal tissue. We will be using biochemical and cell biology approaches to compare the transferrin receptor in a variety of neoplastic cells to the transferrin receptor in normal tissue. In doing so, the physical properties, mechanism of action, binding properties, and control of expression will be studied. Immunological criteria, two-dimensional electrophoretic patterns, and proteolytic digestion patterns will be used in evaluating whether the same protein is expressed in neoplastic tissue as the normal tissues high in transferrin receptor (reticulocytes and placentae). The nature of transferrin binding to its receptor will be studied using a soluble receptor assay. The binding of iron-carrying serum proteins to the transferrin receptor will be evaluated using competitive inhibition experiments. The receptor-transferrin binding process and the fate of the transferrin receptor after transferrin binding will be examined using fluorescently labeled antireceptor IgG preparations and subcellular fractionation techniques. The control of the expression of the transferrin receptor will be examined on neoplastic cell lines where proliferation and iron requirements can be varied independently and on normal human lymphocytes which are capable of mitogenic activation. The expression of the transferrin receptor with respect to cell cycle will be evaluated by using fluorescent-activated cell sorting. The goals of these studies are to define the transferrin receptor and its function and expression in normal and neoplastic cells. This would be helpful in evaluating the feasibility of using it as a target for controlling proliferating cells. (A)